Phase I and pharmacokinetic evaluation of all-trans-retinoic acid in pediatric patients with cancer.

PURPOSE: Recent reports of the dramatic antitumor effect of all-trans-retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have renewed interest in the oncologic indications for retinoids. Furthermore, a variety of pediatric tumors are responsive to RA in vitro, which provides additional rationale for a phase I evaluation of RA in children with cancer that is refractory to standard therapy. PATIENTS AND METHODS: A phase I trial of RA administered orally twice daily for 28-day treatment courses was performed. Cohorts of at least three pediatric cancer patients were entered at successive RA dose levels (from 45 to 80 mg/m2/d) until dose-limiting toxicity (DLT) was consistently observed. RESULTS: The maximum-tolerated dose (MTD) of RA was 60 mg/m2/d. Three of eight patients at the 80-mg/m2/d dose level developed reversible pseudotumor cerebri that necessitated discontinuation of the agent. Both patients with APL achieved complete remission (CR), whereas no patients with solid tumors had objective responses. Pharmacokinetic studies demonstrated a relatively short terminal half-life for RA (45 minutes), with diminution in plasma levels after chronic dosing. CONCLUSIONS: The MTD and recommended phase II dose for RA in children is 60 mg/m2/d given twice daily. Reversible CNS toxicity related to RA-induced pseudotumor cerebri is dose-limiting. Two children with APL achieved a CR to RA, which supports the inclusion of pediatric patients in clinical trials that evaluate the use of RA for patients with APL.

High- versus low-top shoes for the prevention of ankle sprains in basketball players. A prospective randomized study.

Using a prospective, randomized experimental design, 622 college intramural basketball players were stratified by a previous history of ankle sprains to wear a new pair of either high-top, high-top with inflatable air chambers, or low-top basketball shoes during all games for a complete season. Subjects were asked to complete a history questionnaire and were given a complete ankle examination. They were allowed to wear these shoes only during basketball competition. Followed over the course of a 2-month intramural season, 15 ankle injuries occurred during 39,302 minutes of player-time: 7 in high-top shoes, 4 in low-top shoes, and 4 in high-top shoes with inflatable air chambers. The injury rates (injuries per player-minute) were 4.80 x 10(-4) in high-top shoes, 4.06 x 10(-4) in low-top shoes, and 2.69 x 10(-4) in high-top shoes with inflatable air chambers. There was no significant difference among these 3 groups, leading to the conclusion that there is no strong relationship between shoe type and ankle sprains.

Pneumocystis carinii and Mycobacterium avium-intracellulare infection of the choroid.

It has been hypothesized that coinfection with mycobacteria occurs in patients with Pneumocystis carinii choroiditis, but cases demonstrating ocular infection by both organisms have not been reported. This study reports the case of a patient with P. carinii choroiditis who was treated with intravenous trimethoprim and sulfamethoxazole, followed by intravenous trimethoprim and dapsone. The choroidal lesions failed to resolve despite 6 weeks of treatment, and the patient died from massive pulmonary infection caused by P. carinii, Mycobacterium avium-intracellulare, and cytomegalovirus infections. Ocular histologic and electron microscopic examinations revealed choroidal infection by both P. carinii and M. avium-intracellulare. Serum levels of sulfamethoxazole were below the recommended therapeutic range for treating P. carinii infection during the first week of therapy, but adequate drug levels were subsequently obtained. Failure of choroidal lesions of P. carinii to resolve in some cases may suggest insufficient antimicrobial levels in the blood or raise the possibility of coexistent M. avium-intracellulare or other opportunistic infection.